TH11522B - Quinuclidine derivatives - Google Patents

Abstract

Compounds of the formula (chemical formula), where R1 is methoxy and R2, can be selected independently from a group containing isopropyl, ter-butyl, methyl, ethyl and checkbut. Til And the pharmacologically acceptable salt of this compound. These compounds Is an antagonist of substance P and is useful in the treatment of Gastrointestinal Disease, CNS Disease and Patent Drug Pain

Claims (1)

1. Compounds with the formula (chemical formula) where R1 is methoxy, and R2 is selected from a group containing isopropyl, ter-butyl, methyl ethyl and check-. Butyl 2. Compound claim 1, where the compound was selected from the group containing (2S, 3S) -N- (5-isopropyl-2-meth). Thoxyphenyl) methyl-2-diphenylmethyl-1-azabycloid [2.2.2] octan-3-amine (2S, 3S) -N- (5-ethyl-2-methoxyphenyl) methyl-2-diphenyl-methyl-1-azabisyclo [2.2.2] octan-3-A Amine (2S, 3S) -N- (5- isopropyl-2-methoxyphenyl) methyl-2-diphenylmethyl-1-azabycloid [2.2.2] octan-3-amine (2S, 3S) -N- (5-methyl-2-methoxyphenyl) methyl-2-diphenylmene Thyl-1-azabisyclo [2.2.2] octan-3-amine (2S, 3S) -N- (5-tert-bityl-2-methoxyphosphate) Anil) methyl-2-diphenylmethyl-1-azabycloid, [2.2.2] octan-3-amine and (2S, 3S) -N- (5- Check-butyl-2-methoxyphenyl) methyl-2-diphenylmethyl-1-azabisyclo [2.2.2] octan-3-a Mean And the pharmacologically acceptable salt of this compound 3. (2S, 3S) -N- (5- isodropyl-2- (methoxyphenyl) methyl-2-diphenol) Nylmethyl-1-azabisyclo [2.2.2] octan-3-amine methane sulfonate 4. Pharmaceutical components Or prevention of conditions selected from those containing inflammatory diseases Anxiety Ulcerative colitis, depression or insomnia, psychosis, pain, allergies, gastrointestinal disorders Abnormality of excessive sensitivity High tension Diseases involving selective tube compression Myositis and collagen disease, sompathetic neuropathy, reflex, addiction disorder Physical disorders are related to stress. Peripheral neuropathy Skeletal membranes of the brain and spinal cord Pathological disorders, disorders involving immunity-enhancement or suppression, and rheumatic disease in mammals. It consists of a compound according to claim 1 in quantities effective in the prevention or treatment of such condition and a pharmaceutical carrier of 5. Compounds of Formula 1 or the pharmaceutical salts of that substance. In accordance with claim 1 for medicinal use 6. Use of a compound of Formula I or a pharmaceutical salt of that substance for the manufacture of drugs for the treatment or prevention of selected conditions from the inflammatory disease, anxiety disorder group. Colitis, depression, or insomnia, psychosis, pain, allergies, chronic respiratory failure. The normal skin's sensitivity to excess. High tension Diseases involving selective tube compression Myositis and collagen disease, sompathetic nerve misalignment, reflex Addiction disorder Physical disorders are related to stress. Peripheral neuropathy Neurological membranes of the brain and spinal cord. Neurological disorders. Disorders related to Immune enhancement Or suppression and rheumatic disease in mammals. 7. Methods for opposite effect of substance P in mammals. 8. The use of a compound of Formula I or a chemically acceptable salt of that substance. For the manufacture of pharmaceutical machines 9. Pharmaceutical mixtures for the treatment or prevention of conditions in mammals. Therapeutic or prophylactic treatment that affects or helps to reduce the neurotransmitter P of the compound P containing the compound P, as in claim 1, in the opposite effect of P at the receptor position. Pter of this substance. And pharmaceutical carrier acceptable 1 0. Pharmaceutical mixtures for the treatment or prevention of conditions in mammals. Therapeutic or prophylactic treatment that affects or assists the reduction of the neurotransmitter P of P containing compounds as described in claim 1 or the pharmaceutical salts of this substance. In the quantities effective in treating or preventing such conditions and pharmacologically acceptable carriers 1 1. The compound preparation process (chemical formula) where R1 is methoxy and R2 was selected from the iso-containing group. Propyl, tert-butyl, methyl ethyl and check-butyl. And the pharmaceutical salt of this compound. Which consists of compounding of formulas (chemical formulas) with stereotypes, misty as the required compounds of formula III. To eliminate methoxybenzyl group by hydrolytic or hydrogenolytic To make a corresponding compound of a formula (chemical formula) having the same steariochemistry The compound of Formula III is then reacted to form with the aldehyde of the formula (chemical formula) in the presence of reducing agents 1 2. Process as in claim 11, where the reaction between Compounds of Formula III and IV, as in the claim 11 with a drying agent Or by using a device designed to have an aciotropic separation of the resulting water to produce the formula (chemical formula) imine, and then react the imine of the formula V with the reducing agent, which 1 3 The process for preparing the compound Formula I as defined in claim 11 consists of applying the compound of Formula II as defined in claim 11. With the stereochemistry, as well as the desired compound of Formula I, acts to eliminate the methoxybenzyl group by hydrolytics to form the compound of Formula III as defined in claim 11 with The stereocyte mystery is the same as the required compound of Formula I and reacts to the resulting compound Formula III with the compound of the formula (chemical formula), where L is the loosened group 1 4. The process for preparing the formula I compound is as follows: Defined in claim 11, it includes the compounding of Formula II as defined in claim 11. With the stereochemistry, as well as the desired compound of Formula I, acts to eliminate the methoxybenzyl group by hydrolytics to form the compound of Formula III as defined in claim 11 with The stereocyte mystery is the same as the required compound of Formula I and reacts to the resulting compound Formula III with the compound compound (chemical formula), where L is the loosened group 1. 5. The process for preparing the formula compound. I, as defined in claim 11, consists of taking the compound formula II as defined in claim 11. The presence of stereochemistry, as well as the desired compound of formula I, acts to eliminate the methoxyl benzyl group by hydrolytic agents to form the formula compound. III, as defined in claim 11, with the stereoscopic mystery of the desired compound of formula I and reacts to the resulting compound of formula (chemical formula), where L is the loosened group. out Or Imida Sol And then reducing the amide obtained 1. 6. The process for preparing the compound Formula I as defined in claim 11 consists of the use of the compound of Formula II as defined in claim 11. With the stereochemistry, as well as the desired compound of Formula I, acts to eliminate the methoxybenzyl group by hydrolytics to form the compound of Formula III as defined in claim 11 with The stereoscopic mystery is the same as the required compound of Formula I and reacts to the resulting compound Formula III with the constituents of the formula (chemical formula), where L is the detached group. Or Imida Sol And then reducing the resulting amide 1 7.Process as in claim 11-16, one of which also consists of the conversion of the resulting formula I compound into a pharmacologically acceptable salt of the compound 1. 8. Process As in claim 11-17, any one in which the compound prepared from the process is a compound selected from a group containing (2S, 3S) -N- (5- Isopropyl L-2-methoxyphenyl) methyl-2-diphenylmethyl-1-azabycloid [2.2.2] octan-3-amine (2S, 3S) -N- (5-methyl-2-methoxyphenyl) methyl-2-diphenyl-methyl-1-azabiclo [2.2.2] Instead of -3-amine (2S, 3S) -N- (5-ethyl-2-methoxyphenyl) methyl-2-diphenylmethyl-1-aca. Bicyclol [2.2.2], octan-3-amine (2S, 3S) -N- (5-isopropyl-2-methoxyphenyl) methyl-2- Diphenylmethyl-1-azabycloid [2.2.2] octan-3-amine (2S, 3S) -N- (5-tert-butyl-2- Methoxyphenyl), methyl-2-diphenyl-methyl-1-azabycloid, [2.2.2] octan-3-amine and (2S, 3S) - N- (5-check-butyl-2-methoxyphenyl) methyl-2-diphenyl-methyl-1-azabiclo [2.2.2] oc Instead of -3-amines And the pharmacologically acceptable salts of the compound 1 9. Process as in claim 17 where the compound prepared by the aforementioned process is (2S, 3S) -N- (5-isopropyl- 2-methoxyphenyl) methyl-2-diphenylmethyl-1-azabycloid [2.2.2] octan-3-amine methane. Phonate 2 0. Process as in claim 17 where the compound prepared by the process is (2S, 3S) -N- (5-isopropyl-2-methoxifenyl). ) Methyl-2-diphenylmethyl-1-azabycloid [2.2.2] octan-3-amine amine Dihydrochloride 2 1. (2S, 3S) -N- (5- isopropyl-2-methoxyphenyl) methyl-2-diphenylmethyl-1-azabyclo [2.2.2] octan-3-amine dihydrochloride